Isozyme changes have been described for a number of enzyme systems, including the glycolytic enzyme pyruvate kinase in rat and human neoplastic tissues. By the parameter of electrophoretic mobility, a number of these changes are consistent with a theory that the neoplastic process represents a regression to the embryonic state brought about by repression of genes active in the adult differentiated cell and derepression of the corresponding fetal genes. The parameter is satisfactory only for the purposes of inference and speculation and the theory must be tested by more critical examination and comparison of gene products from normal and neoplastic tissues. We are in a unique position to obtain this evidence for human pyruvate kinase, which plays a central role in the energy production of malignant tissues. The order of procedure will be: 1. Electrophoretic examination of pyruvate kinase from human adult, fetal and neoplastic tissues. 2. Kinetic comparison of the enzyme from these tissues after partial purification. 3. Immunological evaluation of the changes using antisera against the human adult isozymes. 4. Purification of the pyruvate kinase isozyme typical of tumor tissue. 5. Comparison of this isozyme with the human erythrocyte, human muscle, and human kidney isozymes, which we have already purified, in sufficient detail to definitely establish the molecular nature of the isozyme change in human neoplastic tissue.